MicroRNAs: powerful new regulators of heart disease and provocative therapeutic targets.

MicroRNAs act as negative regulators of gene expression by inhibiting the translation or promoting the degradation of target mRNAs. Recent studies have revealed key roles of microRNAs as regulators of the growth, development, function, and stress responsiveness of the heart, providing glimpses of undiscovered regulatory mechanisms and potential therapeutic targets for the treatment of heart disease.

[1]  J. Hoffman,et al.  Incidence of congenital heart disease: II. Prenatal incidence , 1995, Pediatric Cardiology.

[2]  Oliver H. Tam,et al.  Characterization of Dicer-deficient murine embryonic stem cells. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[3]  Jian-Fu Chen,et al.  Expression of microRNAs is dynamically regulated during cardiomyocyte hypertrophy. , 2007, Journal of molecular and cellular cardiology.

[4]  Michael T. McManus,et al.  The RNaseIII enzyme Dicer is required for morphogenesis but not patterning of the vertebrate limb. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[5]  R. Quaife,et al.  Coordinate Changes in Myosin Heavy Chain Isoform Gene Expression Are Selectively Associated With Alterations in Dilated Cardiomyopathy Phenotype , 2002, Molecular medicine.

[6]  V. Kim,et al.  The nuclear RNase III Drosha initiates microRNA processing , 2003, Nature.

[7]  J. Castle,et al.  Microarray analysis shows that some microRNAs downregulate large numbers of target mRNAs , 2005, Nature.

[8]  Edwin Cuppen,et al.  The microRNA-producing enzyme Dicer1 is essential for zebrafish development , 2003, Nature Genetics.

[9]  Jian-Fu Chen,et al.  The role of microRNA-1 and microRNA-133 in skeletal muscle proliferation and differentiation , 2006, Nature Genetics.

[10]  Thomas Thum,et al.  MicroRNAs in the Human Heart: A Clue to Fetal Gene Reprogramming in Heart Failure , 2007, Circulation.

[11]  E. Morkin Control of cardiac myosin heavy chain gene expression , 2000, Microscopy research and technique.

[12]  M. Byrom,et al.  Antisense inhibition of human miRNAs and indications for an involvement of miRNA in cell growth and apoptosis , 2005, Nucleic acids research.

[13]  Karl T Kelsey,et al.  MicroRNA responses to cellular stress. , 2006, Cancer research.

[14]  S. Hammond,et al.  MicroRNAs as oncogenes. , 2006, Current opinion in genetics & development.

[15]  Tyler Risom,et al.  Evolutionary conservation of microRNA regulatory circuits: an examination of microRNA gene complexity and conserved microRNA-target interactions through metazoan phylogeny. , 2007, DNA and cell biology.

[16]  Shridar Ganesan,et al.  Dicer-deficient mouse embryonic stem cells are defective in differentiation and centromeric silencing. , 2005, Genes & development.

[17]  E. Olson,et al.  A signature pattern of stress-responsive microRNAs that can evoke cardiac hypertrophy and heart failure , 2006, Proceedings of the National Academy of Sciences.

[18]  Anton J. Enright,et al.  Requirement of bic/microRNA-155 for Normal Immune Function , 2007, Science.

[19]  K. Kosik,et al.  MicroRNA-21 is an antiapoptotic factor in human glioblastoma cells. , 2005, Cancer research.

[20]  Michael T. McManus,et al.  Dysregulation of Cardiogenesis, Cardiac Conduction, and Cell Cycle in Mice Lacking miRNA-1-2 , 2007, Cell.

[21]  I. Klein Thyroid hormone and cardiac contractility. , 2003, The American journal of cardiology.

[22]  Yong Zhao,et al.  Serum response factor regulates a muscle-specific microRNA that targets Hand2 during cardiogenesis , 2005, Nature.

[23]  G. Hannon,et al.  Processing of primary microRNAs by the Microprocessor complex , 2004, Nature.

[24]  K. Fujiwara,et al.  ECM remodeling in hypertensive heart disease. , 2007, The Journal of clinical investigation.

[25]  Yanjie Lu,et al.  Retracted: Novel approaches for gene‐specific interference via manipulating actions of microRNAs: Examination on the pacemaker channel genes HCN2 and HCN4 , 2007, Journal of cellular physiology.

[26]  R Wilders,et al.  Gap junctions in cardiovascular disease. , 2000, Circulation research.

[27]  T. Soukup,et al.  Influence of thyroid status on the differentiation of slow and fast muscle phenotypes. , 2004, Physiological research.

[28]  Anthony K. L. Leung,et al.  Quantitative analysis of Argonaute protein reveals microRNA-dependent localization to stress granules , 2006, Proceedings of the National Academy of Sciences.

[29]  H. Cho,et al.  Selective Inhibition of Inward Rectifier K+ Channels (Kir2.1 or Kir2.2) Abolishes Protection by Ischemic Preconditioning in Rabbit Ventricular Cardiomyocytes , 2004, Circulation research.

[30]  R. Russell,et al.  Animal MicroRNAs Confer Robustness to Gene Expression and Have a Significant Impact on 3′UTR Evolution , 2005, Cell.

[31]  J. Hoffman,et al.  Incidence of congenital heart disease: I. Postnatal incidence , 1995, Pediatric Cardiology.

[32]  M. Stoffel,et al.  Specificity, duplex degradation and subcellular localization of antagomirs , 2007, Nucleic acids research.

[33]  A. Pasquinelli,et al.  Regulation by let-7 and lin-4 miRNAs Results in Target mRNA Degradation , 2005, Cell.

[34]  Chaoqian Xu,et al.  The muscle-specific microRNA miR-1 regulates cardiac arrhythmogenic potential by targeting GJA1 and KCNJ2 , 2011, Nature Medicine.

[35]  B. Bruneau,et al.  The Homeodomain Transcription Factor Irx5 Establishes the Mouse Cardiac Ventricular Repolarization Gradient , 2005, Cell.

[36]  L. Leinwand,et al.  Myosin heavy chain gene expression in human heart failure. , 1997, The Journal of clinical investigation.

[37]  J. Robbins,et al.  Impact of beta-myosin heavy chain expression on cardiac function during stress. , 2004, Journal of the American College of Cardiology.

[38]  L. Leinwand,et al.  Myosin heavy chain isoform expression in the failing and nonfailing human heart. , 2000, Circulation research.

[39]  D. Reinberg,et al.  PARP-1 determines specificity in a retinoid signaling pathway via direct modulation of mediator. , 2005, Molecular cell.

[40]  C. Croce,et al.  MicroRNA-133 controls cardiac hypertrophy , 2007, Nature Medicine.

[41]  E. Olson,et al.  Toward transcriptional therapies for the failing heart: chemical screens to modulate genes. , 2005, The Journal of clinical investigation.

[42]  R. Shiekhattar,et al.  The Microprocessor complex mediates the genesis of microRNAs , 2004, Nature.

[43]  C. Burge,et al.  Conserved Seed Pairing, Often Flanked by Adenosines, Indicates that Thousands of Human Genes are MicroRNA Targets , 2005, Cell.

[44]  J. Molkentin,et al.  Regulation of cardiac hypertrophy by intracellular signalling pathways , 2006, Nature Reviews Molecular Cell Biology.

[45]  Shuomin Zhu,et al.  miR-21-mediated tumor growth , 2007, Oncogene.

[46]  D. Srivastava,et al.  Regulation of cardiac mesodermal and neural crest development by the bHLH transcription factor, dHAND , 1997, Nature Genetics.

[47]  J. S. Janicki,et al.  The relationship between myocardial extracellular matrix remodeling and ventricular function. , 2006, European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery.

[48]  V. Ambros,et al.  The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14 , 1993, Cell.

[49]  N. Rajewsky,et al.  Regulation of the Germinal Center Response by MicroRNA-155 , 2007, Science.

[50]  J. Hoffman,et al.  The incidence of congenital heart disease. , 2002, Journal of the American College of Cardiology.

[51]  R. Roeder,et al.  Thyroid hormone-induced juxtaposition of regulatory elements/factors and chromatin remodeling of Crabp1 dependent on MED1/TRAP220. , 2005, Molecular cell.

[52]  Christine E Seidman,et al.  The genetic basis for cardiac remodeling. , 2005, Annual review of genomics and human genetics.

[53]  N. Rajewsky,et al.  Silencing of microRNAs in vivo with ‘antagomirs’ , 2005, Nature.

[54]  D. Bartel MicroRNAs Genomics, Biogenesis, Mechanism, and Function , 2004, Cell.

[55]  S. Elledge,et al.  Dicer is essential for mouse development , 2003, Nature Genetics.

[56]  Chunxiang Zhang,et al.  MicroRNAs are aberrantly expressed in hypertrophic heart: do they play a role in cardiac hypertrophy? , 2007, The American journal of pathology.

[57]  R. Schwartz,et al.  Embryonic expression of an Nkx2‐5/Cre gene using ROSA26 reporter mice , 2001, Genesis.

[58]  K. McDonald,et al.  Small Amounts of &agr;-Myosin Heavy Chain Isoform Expression Significantly Increase Power Output of Rat Cardiac Myocyte Fragments , 2002, Circulation research.

[59]  K. Furie,et al.  Heart disease and stroke statistics--2007 update: a report from the American Heart Association Statistics Committee and Stroke Statistics Subcommittee. , 2008, Circulation.

[60]  Matthias Merkenschlager,et al.  T cell lineage choice and differentiation in the absence of the RNase III enzyme Dicer , 2005, The Journal of experimental medicine.

[61]  Xiaoxia Qi,et al.  Control of Stress-Dependent Cardiac Growth and Gene Expression by a MicroRNA , 2007, Science.

[62]  Danish Sayed,et al.  MicroRNAs Play an Essential Role in the Development of Cardiac Hypertrophy , 2007, Circulation research.

[63]  B. Reinhart,et al.  The 21-nucleotide let-7 RNA regulates developmental timing in Caenorhabditis elegans , 2000, Nature.